The NIH-sponsored Training Program in Investigative Rheumatology, begun at Yale in 1976, has the philosophy that a portion of biomedical scientists, both MDs and PhDs, should be trained in an environment that focuses upon mechanisms of rheumatologic and immunologic diseases. This belief is grounded in the notion that the challenges involved in understanding these illnesses requires a cohort of investigators whose knowledge and training enable them to span the gaps between basic biology and clinical rheumatology and immunology. Hence, the goals of this program are to attract individuals who are interested in learning about fundamental mechanisms of disease and the applications of this knowledge. The program is focused upon basic investigation, with an emphasis on providing training in immunology, microbiology, and cellular and molecular biology as applied to the clinical understanding of rheumatic diseases;is comprised of both physician and Ph.D. trainees;and has for its training faculty a collaborative group of 29 physician and basic scientists from the Section of Rheumatology and other Sections in the Department of Medicine, and basic investigators from the Section (Department) of Immunobiology. The quality, cohesiveness, and diverse skills of these mentors, along with the skills and the desire of our trainees, are the most important requisites for success of our program. Five trainees (M.D. and Ph.D.) per year are currently supported, with that number requested in this renewal. This request is based upon the success of the program and the number of high quality applicants. M.D. trainees typically perform clinical work in the first year of their fellowship (supported by clinical funds), and then enter research training. The combination of both M.D. and Ph.D. fellows gives the M.D. fellows a much better lab experience, and it exposes the Ph.D. fellows to opportunities to apply their skills to rheumatologic problems. Fellows supported by this Training Grant receive didactic as well as interactive instruction in basic biology, laboratory techniques, clinical investigation and ethical issues in science. This program provides trainees with the foundation in basic and clinical science that will enable them to bridge the differences between basic research and fundamental approaches to understanding rheumatic diseases.